Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control

Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the `resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistanceassociated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised

Monoculture of Leafcutter Ant Gardens

Background -- Leafcutter ants depend on the cultivation of symbiotic Attamyces fungi for food, which are thought to be grown by the ants in single-strain, clonal monoculture throughout the hundreds to thousands of gardens within a leafcutter nest. Monoculture eliminates cultivar-cultivar competition that would select for competitive fungal traits that are detrimental to the ants, whereas polyculture of several fungi could increase nutritional diversity and disease resistance of genetically variable gardens. Methodology/Principal Findings -- Using three experimental approaches, we assessed cultivar diversity within nests of Atta leafcutter ants, which are most likely among all fungus-growing ants to cultivate distinct cultivar genotypes per nest because of the nests' enormous sizes (up to 5000 gardens) and extended lifespans (10–20 years). In Atta texana and in A. cephalotes, we resampled nests over a 5-year period to test for persistence of resident cultivar genotypes within each nest, and we tested for genetic differences between fungi from different nest sectors accessed through excavation. In A. texana, we also determined the number of Attamyces cells carried as a starter inoculum by a dispersing queens (minimally several thousand Attamyces cells), and we tested for genetic differences between Attamyces carried by sister queens dispersing from the same nest. Except for mutational variation arising during clonal Attamyces propagation, DNA fingerprinting revealed no evidence for fungal polyculture and no genotype turnover during the 5-year surveys. Conclusions/Significance -- Atta leafcutter ants can achieve stable, fungal monoculture over many years. Mutational variation emerging within an Attamyces monoculture could provide genetic diversity for symbiont choice (gardening biases of the ants favoring specific mutational variants), an analog of artificial selection.The research was supported by National Science Foundation awards DEB-0920138, DEB-0639879, and DEB-0110073 to UGM; DEB-0949689 to T.R. Schultz, N. Mehdiabadi, and UGM; and a Fellowship (02/05) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico to AR. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vector Culex quinquefasciatus

Culex quinquefasciatus plays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackle C. quinquefasciatus vectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, including C. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistant C. quinquefasciatus was explored to identify candidate genes associated with insecticide resistance. High levels of insecticide resistance were observed for five out of six insecticides tested, with the lowest mortality (0.97%) reported to permethrin, while for DDT, lambdacyhalothrin, bendiocarb and deltamethrin the mortality rate ranged from 1.63–3.29%. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1 h exposure and 58.02% after 4 h. Genotyping of the G119S Ace-1 target site mutation detected a highly significant association (p 8-fold increase vs unexposed controls). These results provide evidence that bendiocarb resistance in Ugandan C. quinquefasciatus is mediated by both target-site mechanisms and over-expression of detoxification enzymes

Development and assessment of a web-based intervention for educating older people on strategies promoting healthy cognition

Divya Vanoh,1,2 Intan Hafizah Ishak,1 Suzana Shahar,1 Zahara Abdul Manaf,1 Nazlena Mohamad Ali,3 Shahrul Azman Mohd Noah4 1Centre for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Dietetics Programme, School of Health Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 3Institute of Visual Informatics (IVI), Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia; 4School of Information Technology, Faculty of Information Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia Background: The increase in the population of aging people has increased the occurrence of cognitive decline leading to predemented stage of dementia, ie, mild cognitive impairment (MCI). The cognitive tools that are web-based have been proven to be useful in decreasing the risk of MCI. Thus, in the present study, an education tool that is web-based, called WESIHAT 2.0©, had been created to educate elderly people about precautionary strategies against MCI.Methodology: WESIHAT 2.0 was devised in a senior-friendly style, which includes touch screen, greater font size, larger icons, and employed multimedia components of text, images, and videos. The components employed in WESIHAT 2.0 were a screening tool called TUA-WELLNESS, 10 guides for memory improvement, health diary, and guide for a healthy menu. This application assessed a group of 73 candidates consisting of elderly people, health professionals, caregivers, and information technology (IT) professionals for 1 month.Results: All the elderly people, caregivers, and 75% of IT and health professionals were satisfied with the subject matter of WESIHAT 2.0. About more than half of the elderly people, caregivers, and IT and health professionals had given a consensus on the comprehensive ease of the terminologies, sentences, images, table, and advice related to diet included in the web application. Proposals for improvements of the web portal included suggestions such as using smaller sentences, using greater font size, adding more images, and avoiding the use of unfamiliar terminologies.Conclusion: WESIHAT 2.0 is a suitable tool for educating older people about the lifestyle modification strategies to slower progression to cognitive impairment, with regard to the significance of expert advice. Keywords: senior-friendly, computer, health, lifestyle, education too